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Jennifer S Lawton - One of the best experts on this subject based on the ideXlab platform.
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adenosine triphosphate sensitive potassium channel kir subunits implicated in cardioprotection by diazoxide
Journal of the American Heart Association, 2015Co-Authors: Matthew C. Henn, Carol M Makepeace, Richard B. Schuessler, Evelyn M. Kanter, Colin G. Nichols, Burhan M Janjua, Jennifer S LawtonAbstract:Background ATP‐sensitive potassium (KATP) channel openers provide cardioprotection in multiple models. Ion flux at an unidentified Mitochondrial KATP channel has been proposed as the mechanism. The renal outer medullary kidney potassium channel subunit, potassium inward rectifying (Kir)1.1, has been implicated as a Mitochondrial channel pore‐forming subunit. We hypothesized that subunit Kir1.1 is involved in cardioprotection (maintenance of Volume homeostasis and contractility) of the KATP channel opener diazoxide (DZX) during stress (exposure to hyperkalemic cardioplegia [CPG]) at the myocyte and Mitochondrial levels. Methods and Results Kir subunit inhibitor Tertiapin Q (TPN‐Q) was utilized to evaluate response to stress. Mouse ventricular Mitochondrial Volume was measured in the following groups: isolation buffer; 200 μmol/L of ATP; 100 μmol/L of DZX+200 μmol/L of ATP; or 100 μmol/L of DZX+200 μmol/L of ATP+TPN‐Q (500 or 100 nmol/L). Myocytes were exposed to Tyrode's solution (5 minutes), test solution (Tyrode's, cardioplegia [CPG], CPG+DZX, CPG+DZX+TPN‐Q, Tyrode's+TPN‐Q, or CPG+TPN‐Q), N=12 for all (10 minutes); followed by Tyrode's (5 minutes). Volumes were compared. TPN‐Q, with or without DZX, did not alter Mitochondrial or myocyte Volume. Stress (CPG) resulted in myocyte swelling and reduced contractility that was prevented by DZX. TPN‐Q prevented the cardioprotection afforded by DZX (Volume homeostasis and maintenance of contractility). Conclusions TPN‐Q inhibited myocyte cardioprotection provided by DZX during stress; however, it did not alter Mitochondrial Volume. Because TPN‐Q inhibits Kir1.1, Kir3.1, and Kir3.4, these data support that any of these Kir subunits could be involved in the cardioprotection afforded by diazoxide. However, these data suggest that Mitochondrial swelling by diazoxide does not involve Kir1.1, 3.1, or 3.4.
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relationship between Mitochondrial matrix Volume and cellular Volume in response to stress and the role of atp sensitive potassium channel
Circulation, 2013Co-Authors: Melissa M Anastacio, Carol M Makepeace, Richard B. Schuessler, Evelyn M. Kanter, Angela D. Keith, Haixia Zhang, Jennifer S LawtonAbstract:Background—Cardiac myocytes demonstrate significant swelling and associated reduced contractility in response to stress that is prevented by the ATP-sensitive potassium channel opener, diazoxide (DZX) via an unknown mechanism. One proposed mechanism of cardioprotection is Mitochondrial matrix swelling. To establish the relationship between Mitochondrial and cellular Volume during stress, this study examined the effect of DZX on Mitochondrial Volume. Methods and Results—Isolated mouse mitochondria were exposed to the following solutions: Tyrode, isolation buffer, cardioplegia (CPG)±DZX±ATP-sensitive potassium channel inhibitor, 5-hydroxydecanoate, and metabolic inhibition (MI)±DZX±5-hydroxydecanoate. Mitochondrial Volume was measured. DZX resulted in significant Mitochondrial swelling (P<0.0001 versus Tyrode). MI and CPG resulted in significant Mitochondrial swelling compared with baseline Volume. The addition of DZX did not alter the response of Mitochondrial Volume to CPG (P=0.912) but increased swelling...
Carsten Lundby - One of the best experts on this subject based on the ideXlab platform.
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sexual dimorphism of substrate utilization differences in skeletal muscle Mitochondrial Volume density and function
Experimental Physiology, 2018Co-Authors: David Montero, Klavs Madsen, Annekristine Meinildlundby, Fredrik Edin, Carsten LundbyAbstract:NEW FINDINGS: What is the central question of this study? Females rely to a greater extent than males on fat oxidation during exercise. Whether any difference in skeletal muscle Mitochondrial phenotype and oxidative capacity contributes to this sexual dimorphism remains incompletely explored. What is the main finding and its importance? Female prioritization of fat during exercise occurs in parallel to augmented Mitochondrial Volume density and intrinsic fatty acid and lactate oxidation in skeletal muscle fibres compared with males, independently of aerobic exercise capacity. The enlarged metabolic machinery in skeletal muscle of females is associated with lower body size and leg mass. ABSTRACT: Fat oxidation during exercise is greater in females than in males. We sought to determine whether sex differences in substrate metabolism are paralleled by distinct skeletal muscle Mitochondrial Volume density and oxidative capacity. Whole-body substrate (fat and carbohydrate) utilization during submaximal treadmill running was assessed, and skeletal muscle biopsies were taken to determine Mitochondrial Volume density and function in healthy young females (n = 12) and males (n = 12) matched by aerobic exercise capacity and exercise performance. Females presented a lower respiratory exchange ratio (0.87 ± 0.04 versus 0.91 ± 0.04, P = 0.023) and whole-body carbohydrate oxidation (27.8 ± 8.3 versus 35.8 ± 6.5 mg kg-1 min-1 , P = 0.027), whereas fat oxidation was higher (8.7 ± 2.8 versus 5.9 ± 2.6 mg kg-1 min-1 , P = 0.034) during submaximal exercise compared with males. In skeletal muscle biopsies, females demonstrated augmented Mitochondrial Volume density (7.51 ± 1.77 versus 5.90 ± 1.72%, P = 0.035) and oxidative capacity for fatty acid [36.6 ± 12.8 versus 24.5 ± 7.3 pmol O2 s-1 (mg wet weight)-1 , P = 0.009] and lactate [71.1 ± 24.4 versus 53.2 ± 14.6 pmol O2 s-1 (mg wet weight)-1 , P = 0.040]. No sex differences in respiratory exchange ratio, whole-body fat oxidation and skeletal muscle variables were detected when adjusted for anthropometric variables including body mass or leg mass, which were lower in females. In conclusion, female prioritization of fat over carbohydrate oxidation during exercise is underpinned by augmented body size-related Mitochondrial Volume density, fatty acid and lactate oxidative capacity in skeletal muscle fibres.
Buttemer, William A. - One of the best experts on this subject based on the ideXlab platform.
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High muscle Mitochondrial Volume and aerobic capacity in a small marsupial (Sminthopsis crassicaudata) reveals flexible links between energy-use levels in mammals
'The Company of Biologists', 2013Co-Authors: Dawson, Terence J, Webster, Koa N, Lee Enhua, Buttemer, William A.Abstract:We investigated the muscle structure-function relationships that underlie the aerobic capacity of an insectivorous, small (~15?g) marsupial, Sminthopsis crassicaudata (Family: Dasyuridae), to obtain further insight into energy use patterns in marsupials relative to those in placentals, their sister clade within the Theria (advanced mammals). Disparate hopping marsupials (Suborder Macropodiformes), a kangaroo (Macropus rufus) and a rat-kangaroo (Bettongia penicillata), show aerobic capabilities as high as those of \u27athletic\u27 placentals. Equivalent muscle Mitochondrial Volumes and cardiovascular features support these capabilities. We examined S. crassicaudata to determine whether highly developed aerobic capabilities occur elsewhere in marsupials, rather than being restricted to the more recently evolved Macropodiformes. This was the case. Treadmill-trained S. crassicaudata attained a maximal aerobic metabolic rate (VO2,max or MMR) of 272ml O2min-1kg -1 (N=8), similar to that reported for a small (?20g), \u27athletic\u27 placental, Apodemus sylvaticus, 264ml O2min -1kg-1. Hopping marsupials have comparable aerobic levels when body mass variation is considered. Sminthopsis crassicaudata has a basal metabolic rate (BMR) about 75% of placental values but it has a notably large factorial aerobic scope (fAS) of 13, elevated fAS also features in hopping marsupials. The VO2,max of S. crassicaudata was supported by an elevated total muscle Mitochondrial Volume, which was largely achieved through high muscle Mitochondrial Volume densities, Vv(mt,f), the mean value being 14.0±1.33%. These data were considered in relation to energy use levels in mammals, particularly field metabolic rate (FMR). BMR is consistently lower in marsupials, but this is balanced by a high fAS, such that marsupial MMR matches that of placentals. However, FMR shows different mass relationships in the two clades, with the FMR of small (<, 125 g) marsupials, such as S. crassicaudata, being higher than that in comparably sized placentals, with the reverse applying for larger marsupials. The flexibility of energy output in marsupials provides explanations for this pattern. Overall, our data refute widely held notions of mechanistically closely linked relationships between body mass, BMR, FMR and MMR in mammals generally
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High muscle Mitochondrial Volume and aerobic capacity in a small marsupial (Sminthopsis crassicaudata) reveals flexible links between energy-use levels in mammals
'The Company of Biologists', 2013Co-Authors: Dawson, Terence J, Webster, Koa N, Lee Enhua, Buttemer, William A.Abstract:We investigated the muscle structure-function relationships that underlie the aerobic capacity of an insectivorous, small (~15 g) marsupial, Sminthopsis crassicaudata (Family: Dasyuridae), to obtain further insight into energy use patterns in marsupials relative to those in placentals, their sister clade within the Theria (advanced mammals). Disparate hopping marsupials (Suborder Macropodiformes), a kangaroo (Macropus rufus) and a rat-kangaroo (Bettongia penicillata), show aerobic capabilities as high as those of 'athletic' placentals. Equivalent muscle Mitochondrial Volumes and cardiovascular features support these capabilities. We examined S. crassicaudata to determine whether highly developed aerobic capabilities occur elsewhere in marsupials, rather than being restricted to the more recently evolved Macropodiformes. This was the case. Treadmill-trained S. crassicaudata attained a maximal aerobic metabolic rate (VO2,max or MMR) of 272ml O₂min⁻¹kg ⁻¹ (N=8), similar to that reported for a small (~20g), 'athletic' placental, Apodemus sylvaticus, 264ml O₂min⁻¹kg⁻¹. Hopping marsupials have comparable aerobic levels when body mass variation is considered. Sminthopsis crassicaudata has a basal metabolic rate (BMR) about 75% of placental values but it has a notably large factorial aerobic scope (fAS) of 13; elevated fAS also features in hopping marsupials. The VO2,max of S. crassicaudata was supported by an elevated total muscle Mitochondrial Volume, which was largely achieved through high muscle Mitochondrial Volume densities, Vv(mt,f), the mean value being 14.0±1.33%. These data were considered in relation to energy use levels in mammals, particularly field metabolic rate (FMR). BMR is consistently lower in marsupials, but this is balanced by a high fAS, such that marsupial MMR matches that of placentals. However, FMR shows different mass relationships in the two clades, with the FMR of small (
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High muscle Mitochondrial Volume and aerobic capacity in a small marsupial (Sminthopsis crassicaudata) reveals flexible links between energy-use levels in mammals
'Sociological Research Online', 2012Co-Authors: Dawson Terence, Lee Enhua, Webster Koa, Buttemer, William A.Abstract:We investigated the muscle structure–function relationships that underlie the aerobic capacity of an insectivorous, small (~15 g) marsupial, Sminthopsis crassicaudata (Family: Dasyuridae), to obtain further insight into energy use patterns in marsupials relative to those in placentals, their sister clade within the Theria (advanced mammals). Disparate hopping marsupials (Suborder Macropodiformes), a kangaroo (Macropus rufus) and a rat-kangaroo (Bettongia penicillata), show aerobic capabilities as high as those of ‘athletic’ placentals. Equivalent muscle Mitochondrial Volumes and cardiovascular features support these capabilities. We examined S. crassicaudata to determine whether highly developed aerobic capabilities occur elsewhere in marsupials, rather than being restricted to the more recently evolved Macropodiformes. This was the case. Treadmill-trained S. crassicaudata attained a maximal aerobic metabolic rate ( or MMR) of 272 ml O2 min−1 kg−1 (N=8), similar to that reported for a small (~20 g), ‘athletic’ placental, Apodemus sylvaticus, 264 ml O2 min−1 kg−1. Hopping marsupials have comparable aerobic levels when body mass variation is considered. Sminthopsis crassicaudata has a basal metabolic rate (BMR) about 75% of placental values but it has a notably large factorial aerobic scope (fAS) of 13; elevated fAS also features in hopping marsupials. The of S. crassicaudata was supported by an elevated total muscle Mitochondrial Volume, which was largely achieved through high muscle Mitochondrial Volume densities, Vv(mt,f), the mean value being 14.0±1.33%. These data were considered in relation to energy use levels in mammals, particularly field metabolic rate (FMR). BMR is consistently lower in marsupials, but this is balanced by a high fAS, such that marsupial MMR matches that of placentals. However, FMR shows different mass relationships in the two clades, with the FMR of small (\u3c125 \u3eg) marsupials, such as S. crassicaudata, being higher than that in comparably sized placentals, with the reverse applying for larger marsupials. The flexibility of energy output in marsupials provides explanations for this pattern. Overall, our data refute widely held notions of mechanistically closely linked relationships between body mass, BMR, FMR and MMR in mammals generally
Michael C. Hogan - One of the best experts on this subject based on the ideXlab platform.
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alterations in skeletal muscle indicators of Mitochondrial structure and biogenesis in patients with type 2 diabetes and heart failure effects of epicatechin rich cocoa
Clinical and Translational Science, 2012Co-Authors: Guy A. Perkins, R Pam M D Taub, Israel Ramirezsanchez, Theodore P Ciaraldi, Anne N Murphy, Robert K Naviaux, Michael C. HoganAbstract:(-)-Epicatechin (Epi), a flavanol in cacao stimulates Mitochondrial Volume and cristae density and protein markers of skeletal muscle (SkM) Mitochondrial biogenesis in mice. Type 2 diabetes mellitus (DM2) and heart failure (HF) are diseases associated with defects in SkM Mitochondrial structure/function. A study was implemented to assess perturbations and to determine the effects of Epi-rich cocoa in SkM Mitochondrial structure and mediators of biogenesis. Five patients with DM2 and stage II/III HF consumed dark chocolate and a beverage containing approximately 100 mg of Epi per day for 3 months. We assessed changes in protein and/or activity levels of oxidative phosphorylation proteins, porin, mitofilin, nNOS, nitric oxide, cGMP, SIRT1, PGC1α, Tfam, and mitochondria Volume and cristae abundance by electron microscopy from SkM. Apparent major losses in normal mitochondria structure were observed before treatment. Epi-rich cocoa increased protein and/or activity of mediators of biogenesis and cristae abundance while not changing Mitochondrial Volume density. Epi-rich cocoa treatment improves SkM Mitochondrial structure and in an orchestrated manner, increases molecular markers of Mitochondrial biogenesis resulting in enhanced cristae density. Future controlled studies are warranted using Epi-rich cocoa (or pure Epi) to translate improved Mitochondrial structure into enhanced cardiac and/or SkM muscle function.
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alterations in skeletal muscle indicators of Mitochondrial structure and biogenesis in patients with type 2 diabetes and heart failure effects of epicatechin rich cocoa
Clinical and Translational Science, 2012Co-Authors: R Pam M D Taub, Michael C. Hogan, Guy A. Perkins, Israel Ramirezsanchez, Theodore P Ciaraldi, Anne N Murphy, Robert K Naviaux, S Alan M D Maisel, Robert R HenryAbstract:(-)-Epicatechin (Epi), a flavanol in cacao stimulates Mitochondrial Volume and cristae density and protein markers of skeletal muscle (SkM) Mitochondrial biogenesis in mice. Type 2 diabetes mellitus (DM2) and heart failure (HF) are diseases associated with defects in SkM Mitochondrial structure/function. A study was implemented to assess perturbations and to determine the effects of Epi-rich cocoa in SkM Mitochondrial structure and mediators of biogenesis. Five patients with DM2 and stage II/III HF consumed dark chocolate and a beverage containing approximately 100 mg of Epi per day for 3 months. We assessed changes in protein and/or activity levels of oxidative phosphorylation proteins, porin, mitofilin, nNOS, nitric oxide, cGMP, SIRT1, PGC1α, Tfam, and mitochondria Volume and cristae abundance by electron microscopy from SkM. Apparent major losses in normal mitochondria structure were observed before treatment. Epi-rich cocoa increased protein and/or activity of mediators of biogenesis and cristae abundance while not changing Mitochondrial Volume density. Epi-rich cocoa treatment improves SkM Mitochondrial structure and in an orchestrated manner, increases molecular markers of Mitochondrial biogenesis resulting in enhanced cristae density. Future controlled studies are warranted using Epi-rich cocoa (or pure Epi) to translate improved Mitochondrial structure into enhanced cardiac and/or SkM muscle function. Clin Trans Sci 2012; Volume 5: 43–47
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resistance to fatigue of individual xenopus single skeletal muscle fibres is correlated with Mitochondrial Volume density
Experimental Physiology, 2004Co-Authors: Creed M. Stary, Odile Mathieucostello, Michael C. HoganAbstract:The purpose of the present study was to compare the individual fatigue characteristics of isolated single skeletal muscle fibres with their Mitochondrial Volume density (MVD), using direct histological morphometry. Single muscle fibres (n= 14) were microdissected from lumbrical muscle of adult female Xenopus laevis, and force was measured while fibres were stimulated (tetanic contractions of 200 ms trains with 70 Hz stimuli at 9 V) at progressively increasing frequencies (2 min each at 0.25, 0.33, 0.5 and 1 contractions s−1) until fatigue (<50% initial maximal force) had been established. Following the end of the fatigue protocol, MVD was determined by electron microscopy. Time to fatigue varied among the individual fibres from 3.3 to 10 min. MVD of individual fibres ranged from 3.0 to 9.2% and was positively correlated (r= 0.93) with time to fatigue of corresponding fibres. These results, using direct histological measurements of MVD: (1) support on a single cell basis the notion that oxidative capacity is a major determinant of muscle fatigue resistance; and (2) show that the fatigue profile of a single cell can be used to predict oxidative capacity.
Carol M Makepeace - One of the best experts on this subject based on the ideXlab platform.
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adenosine triphosphate sensitive potassium channel kir subunits implicated in cardioprotection by diazoxide
Journal of the American Heart Association, 2015Co-Authors: Matthew C. Henn, Carol M Makepeace, Richard B. Schuessler, Evelyn M. Kanter, Colin G. Nichols, Burhan M Janjua, Jennifer S LawtonAbstract:Background ATP‐sensitive potassium (KATP) channel openers provide cardioprotection in multiple models. Ion flux at an unidentified Mitochondrial KATP channel has been proposed as the mechanism. The renal outer medullary kidney potassium channel subunit, potassium inward rectifying (Kir)1.1, has been implicated as a Mitochondrial channel pore‐forming subunit. We hypothesized that subunit Kir1.1 is involved in cardioprotection (maintenance of Volume homeostasis and contractility) of the KATP channel opener diazoxide (DZX) during stress (exposure to hyperkalemic cardioplegia [CPG]) at the myocyte and Mitochondrial levels. Methods and Results Kir subunit inhibitor Tertiapin Q (TPN‐Q) was utilized to evaluate response to stress. Mouse ventricular Mitochondrial Volume was measured in the following groups: isolation buffer; 200 μmol/L of ATP; 100 μmol/L of DZX+200 μmol/L of ATP; or 100 μmol/L of DZX+200 μmol/L of ATP+TPN‐Q (500 or 100 nmol/L). Myocytes were exposed to Tyrode's solution (5 minutes), test solution (Tyrode's, cardioplegia [CPG], CPG+DZX, CPG+DZX+TPN‐Q, Tyrode's+TPN‐Q, or CPG+TPN‐Q), N=12 for all (10 minutes); followed by Tyrode's (5 minutes). Volumes were compared. TPN‐Q, with or without DZX, did not alter Mitochondrial or myocyte Volume. Stress (CPG) resulted in myocyte swelling and reduced contractility that was prevented by DZX. TPN‐Q prevented the cardioprotection afforded by DZX (Volume homeostasis and maintenance of contractility). Conclusions TPN‐Q inhibited myocyte cardioprotection provided by DZX during stress; however, it did not alter Mitochondrial Volume. Because TPN‐Q inhibits Kir1.1, Kir3.1, and Kir3.4, these data support that any of these Kir subunits could be involved in the cardioprotection afforded by diazoxide. However, these data suggest that Mitochondrial swelling by diazoxide does not involve Kir1.1, 3.1, or 3.4.
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relationship between Mitochondrial matrix Volume and cellular Volume in response to stress and the role of atp sensitive potassium channel
Circulation, 2013Co-Authors: Melissa M Anastacio, Carol M Makepeace, Richard B. Schuessler, Evelyn M. Kanter, Angela D. Keith, Haixia Zhang, Jennifer S LawtonAbstract:Background—Cardiac myocytes demonstrate significant swelling and associated reduced contractility in response to stress that is prevented by the ATP-sensitive potassium channel opener, diazoxide (DZX) via an unknown mechanism. One proposed mechanism of cardioprotection is Mitochondrial matrix swelling. To establish the relationship between Mitochondrial and cellular Volume during stress, this study examined the effect of DZX on Mitochondrial Volume. Methods and Results—Isolated mouse mitochondria were exposed to the following solutions: Tyrode, isolation buffer, cardioplegia (CPG)±DZX±ATP-sensitive potassium channel inhibitor, 5-hydroxydecanoate, and metabolic inhibition (MI)±DZX±5-hydroxydecanoate. Mitochondrial Volume was measured. DZX resulted in significant Mitochondrial swelling (P<0.0001 versus Tyrode). MI and CPG resulted in significant Mitochondrial swelling compared with baseline Volume. The addition of DZX did not alter the response of Mitochondrial Volume to CPG (P=0.912) but increased swelling...